US4124759A - Preparation of auranofin by O-acetylation - Google Patents

Preparation of auranofin by O-acetylation Download PDF

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Publication number
US4124759A
US4124759A US05/812,016 US81201677A US4124759A US 4124759 A US4124759 A US 4124759A US 81201677 A US81201677 A US 81201677A US 4124759 A US4124759 A US 4124759A
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US
United States
Prior art keywords
auranofin
triethylphosphinegold
thio
excess
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
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US05/812,016
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English (en)
Inventor
David T. Hill
Ivan Lantos
Blaine M. Sutton
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Corp
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SmithKline Corp
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Filing date
Publication date
Application filed by SmithKline Corp filed Critical SmithKline Corp
Priority to US05/812,016 priority Critical patent/US4124759A/en
Priority to DK286378A priority patent/DK151031C/da
Priority to JP8044978A priority patent/JPS5414930A/ja
Priority to SE7807450A priority patent/SE7807450L/xx
Application granted granted Critical
Publication of US4124759A publication Critical patent/US4124759A/en
Assigned to SMITHKLINE BECKMAN CORPORATION reassignment SMITHKLINE BECKMAN CORPORATION CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). EFFECTIVE DATE: 03/04/82 Assignors: SMITHKLINE CORPORATION
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H23/00—Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • This invention comprises a method for preparing auranofin, S-triethylphosphinegold 2,3,4,6-tetra-O-acetyl-1-thio- ⁇ -D-glucopyranoside, which involves direct O-acetylation of S-triethylphosphinegold 1-thio- ⁇ -D-glucopyranoside.
  • Auranofin has been described as prepared by a number of synthetic procedures usually by the reaction of the alkali metal salt of 2,3,4,6-tetra-O-acetyl-1-thio- ⁇ -D-glucopyranose with triethylphosphinegold chloride. See U.S. Pat. No. 3,635,945 and J. Med. Chem. 15: 1095 (1972). There is no suggestion in the art of the process here claimed.
  • This process is based on direct O-acetylation of S-triethylphosphinegold 1-thio- ⁇ -D-glucopyranoside using a tertiary organic base and acetic anhydride under moderate conditions.
  • the use of certain traditional O-acylation methods on desacetyl auranofin such as acetyl chloride plus alkali in aqueous miscible solvents causes extensive decomposition of the sugar gold complex which serves as starting material.
  • the process here described comprises reacting S-triethylphosphinegold 1-thio- ⁇ -D-glucopyranoside with an excess of a tertiary organic amine base such as a tertiary heterocyclic amine which has basic characteristics for example pyridine, picoline, lutidine, N-methyl-tetramethylpiperidine, 1,8-bis(dimethylamino)naphthalene or N-methylpiperidine or a triloweralkylamine with similar basic properties such as tributylamine, triamylamine or triethylamine. If the tertiary amine has suitable solvent properties at the temperature of the reaction, such as the preferred pyridine, it may be used in excess as the solvent.
  • a tertiary organic amine base such as a tertiary heterocyclic amine which has basic characteristics for example pyridine, picoline, lutidine, N-methyl-tetramethylpiperidine, 1,8-bis(d
  • a slight to moderate excess of the tertiary amine may be present with an organic solvent in which the starting materials are soluble and to which it is chemically inert.
  • organic solvents are ethyl ether, dioxane, dimethylacetamide, dimethyl sulfoxide, dimethylformamide, benzene, methylene chloride, carbon tetrachloride and chloroform.
  • the solvent or tertiary amine should be as water free as possible for commercial conditions.
  • the phosphinegold complex together with the tertiary organic amine and acetic anhydride in excess, optionally with an inert organic solvent present, are reacted at temperatures ranging from about -25° to the reflux temperature of the reaction mixture. Best results are from 0° to room temperature.
  • the reaction mixture is allowed to stand until the reaction is complete such as overnight for low temperatures to up to 1-2 hours on the steam bath.
  • the time and temperature of the reaction are not particularly crucial to the reaction but low temperatures for longer periods of time such as -25° to 0° for from 6-24 hours give good yields of auranofin.
  • reaction of this invention can be run using acetyl chloride in tertiary base as described above. Usually when acetyl chloride is used a smaller excess of acylating agent is used along with correspondingly lower reaction temperatures.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pain & Pain Management (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Rheumatology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Saccharide Compounds (AREA)
  • Steroid Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US05/812,016 1977-06-30 1977-06-30 Preparation of auranofin by O-acetylation Expired - Lifetime US4124759A (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US05/812,016 US4124759A (en) 1977-06-30 1977-06-30 Preparation of auranofin by O-acetylation
DK286378A DK151031C (da) 1977-06-30 1978-06-26 Fremgangsmaade til fremstilling af auranofin ved o-acetylering
JP8044978A JPS5414930A (en) 1977-06-30 1978-06-29 Process for preparing golddcontaining compound
SE7807450A SE7807450L (sv) 1977-06-30 1978-06-30 Framstellning av auranofin genom o-acetylering

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US05/812,016 US4124759A (en) 1977-06-30 1977-06-30 Preparation of auranofin by O-acetylation

Publications (1)

Publication Number Publication Date
US4124759A true US4124759A (en) 1978-11-07

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ID=25208231

Family Applications (1)

Application Number Title Priority Date Filing Date
US05/812,016 Expired - Lifetime US4124759A (en) 1977-06-30 1977-06-30 Preparation of auranofin by O-acetylation

Country Status (4)

Country Link
US (1) US4124759A (enrdf_load_stackoverflow)
JP (1) JPS5414930A (enrdf_load_stackoverflow)
DK (1) DK151031C (enrdf_load_stackoverflow)
SE (1) SE7807450L (enrdf_load_stackoverflow)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4201775A (en) * 1979-03-23 1980-05-06 Smithkline Corporation Bis[triethylphosphine)aurio]sulfonium sugars

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3635945A (en) * 1969-10-28 1972-01-18 Smith Kline French Lab Trialkylphosphinegold complexes of 1-beta-d-glucopyranosides
US3843626A (en) * 1968-12-31 1974-10-22 Smithkline Corp Anti-inflammatory compositions containing acylated-b-d-glucopyranosides and methods of using them
US3985727A (en) * 1975-03-28 1976-10-12 Schering Corporation Aminoglycoside antibiotics

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3843626A (en) * 1968-12-31 1974-10-22 Smithkline Corp Anti-inflammatory compositions containing acylated-b-d-glucopyranosides and methods of using them
US3635945A (en) * 1969-10-28 1972-01-18 Smith Kline French Lab Trialkylphosphinegold complexes of 1-beta-d-glucopyranosides
US3985727A (en) * 1975-03-28 1976-10-12 Schering Corporation Aminoglycoside antibiotics

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Sutton et al., J. Med. Chem. 15, 1095 (1972). *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4201775A (en) * 1979-03-23 1980-05-06 Smithkline Corporation Bis[triethylphosphine)aurio]sulfonium sugars

Also Published As

Publication number Publication date
DK151031C (da) 1988-03-07
DK151031B (da) 1987-10-12
SE7807450L (sv) 1979-12-31
JPS6126916B2 (enrdf_load_stackoverflow) 1986-06-23
DK286378A (da) 1978-12-31
JPS5414930A (en) 1979-02-03

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Owner name: SMITHKLINE BECKMAN CORPORATION

Free format text: CHANGE OF NAME;ASSIGNOR:SMITHKLINE CORPORATION;REEL/FRAME:004080/0769

Effective date: 19820304

Owner name: SMITHKLINE BECKMAN CORPORATION, PENNSYLVANIA

Free format text: CHANGE OF NAME;ASSIGNOR:SMITHKLINE CORPORATION;REEL/FRAME:004080/0769

Effective date: 19820304